title: Capsaicin combined with local anesthetics preferentially prolongs sensory/nociceptive block in rat sciatic nerve.
abstract: BACKGROUND
  Transient receptor potential vanilloid 1 channels integrate nociceptive stimuli and are predominantly expressed by unmyelinated C-fiber nociceptors, but not low-threshold mechanoreceptive sensory or motor fibers. A recent report showed that the transient receptor potential vanilloid 1 channel agonist capsaicin allows a hydrophilic quaternary ammonium derivative of lidocaine, QX-314, to selectively block C fibers without motor block. The authors tested whether a similar differential block would be produced using amphipathic N-methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, either alone or together with 0.05% capsaicin, in a rat sciatic nerve block model.
  
  
  METHODS
  Rats (n = 8/group) were anesthetized with sevoflurane, and 0.2 ml of drug was injected either alone or with capsaicin (simultaneously or 10 min later) next to the sciatic nerve in the sciatic notch. Motor function was assessed by the extensor postural thrust. Nociception was evaluated by the nocifensive withdrawal reflex and vocalization evoked by pinch of a skin fold over the lateral metatarsus (cutaneous pain) with a serrated forceps.
  
  
  RESULTS
  N-Methyl amitriptyline, amitriptyline, bupivacaine, or lidocaine, followed by injection of capsaicin 10 min later, each elicited a predominantly nociceptive-specific blockade. In comparison, simultaneous application of each local anesthetic with capsaicin did not elicit a clinically significant differential block, with the exception of N-methyl amitriptyline.
  
  
  CONCLUSIONS
  Both tertiary amine local anesthetics and their quaternary ammonium derivatives can elicit a predominantly sensory/nociceptor selective block when followed by injection of capsaicin. The combined application of transient receptor potential vanilloid 1 channel agonists and various local anesthetics or their quaternary ammonium derivatives is an appealing strategy to achieve a long-lasting differential block in regional analgesia.
authors.affiliation: Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. pgerner@partners.org
authors.forename: Peter
authors.initials: P
authors.lastname: Gerner
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Binshtok
authors.forename: Chi-Fei
authors.initials: CF
authors.lastname: Wang
authors.forename: Nathanael D
authors.initials: ND
authors.lastname: Hevelone
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Bean
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
authors.forename: Ging Kuo
authors.initials: GK
authors.lastname: Wang
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D008297:Male; D009407:Nerve Block / Q000379:methods*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D000779:Anesthetics, Local; D002211:Capsaicin